tbuckley/cabot-search huggingface dataset:
AB0343 LONG-TERM TOCILIZUMAB TREATMENT IN PATIENTS WITH RHEUMATOID ARTHRITIS IN DAILY CLINICAL PRACTICE
Authors: Y. Ono, Y. Hirano
Journal: Annals of the Rheumatic Diseases (2022)

Background Tocilizumab (TCZ) is a humanized anti-IL-6 receptor monoclonal antibody that improves the signs and symptoms of rheumatoid arthritis (RA). In previous clinical trials, long-term outcomes have been increasingly evaluated in daily clinical practice. We report the five-year outcomes of TCZ treatment at our institute. Objectives This retrospective study determined the long-term trends in TCZ use in clinical practice. Methods Data from the Toyohashi RA database (TRAD) were used. The TRAD is single-center retrospective data. Last observation carried forward was used as a complementary method for missing data. Participants were 59 RA patients in whom TCZ therapy was started at our institute from September 2009 to May 2016. Subsequent items, baseline patient characteristics, disease activity, treatment continuation rates of TCZ using the Kaplan-Meier method, reasons for stopping TCZ, concomitant use of methotrexate (MTX) and prednisolone (PSL) were investigated. Results Baseline characteristics at the start of TCZ treatment were 17 men and 42 women with a mean age of 58.6 years (30–81). The mean RA duration was 8.7 years (0–31). The mean SDAI score was 27.9 ± 11.6; the mean DAS28-CRP was 5.0 ± 1.0. CRP was 4.1 ± 3.0 mg/dl and MMP-3 388.3 ± 311.5 ng/ml. Methotrexate (MTX) was administered in 37 patients (62.7%, mean 6.0 mg, mean MTX dose administered in cases, 9.6 mg/week). Prednisolone (PSL) was administered in 37 patients (62.7%, mean 3.6 mg; the mean PSL dose administered in cases 5.7 mg/day). Regarding disease activity, the mean SDAI was 27.9 at baseline; 12.3 at three months; 8.1 at one year; 7.3 at two years; 6.5 at three years; 46.7 at four years; 5.6 at five years, and 5.2 at final observation. The SDAI significantly improved after two years compared to baseline. Remission and low disease activity also significantly improved at one year and gradually improved after one year (Figure 1). The remission rate at the final observation was 55.2%, with an SDAI ≦3.3. TCZ continuation rates were 86.9% at one year, 78.7％ at three years, and 68.9% at five years (Figure 2). TCZ was discontinued due to adverse events in 11 cases (18%), and inadequate efficacy occurred in 9 (14.8%). The adverse events were respiratory infection (5), purulent arthritis (1), infectious endocarditis (1), subarachnoid hemorrhage (1), breast cancer (1), pruritis (1), and skin ulcer (1). Other reasons for discontinuation were dialysis (2), suspension of hospital visits (2), kidney transplant (1), and financial difficulties (1). Concomitant use from baseline to final observation declined from 62.7% to 15.3% for MTX and from 62.7% to 23.7% for PSL. Conclusion Long-term treatment with TCZ was acceptable. We found that with TCZ therapy, the remission and low disease activity rates significantly improved at one year and continued to improve after one year. Treatment persistence was high, but careful monitoring for infection is necessary. Disclosure of Interests None declared
Status of Cardiovascular Health in US Adults and Children Using the American Heart Association’s New “Life’s Essential 8” Metrics: Prevalence Estimates From the National Health and Nutrition Examination Survey (NHANES), 2013 Through 2018
Authors: Donald M. Lloyd-Jones, Hongyan Ning, Darwin Labarthe, LaPrincess Brewer, Garima Sharma, Wayne Rosamond, Randi E. Foraker, Terrie Black, Michael A. Grandner, Norrina B. Allen, Cheryl Anderson, Helen Lavretsky, Amanda M. Perak
Journal: Circulation (2022)

The American Heart Association recently published an updated algorithm for quantifying cardiovascular health (CVH)-the Life's Essential 8 score. We quantified US levels of CVH using the new score.
STAT1 is essential for HSC function and maintains MHCIIhi stem cells that resist myeloablation and neoplastic expansion
Authors: Juan Li, Matthew J. Williams, Hyun Jung Park, Hugo P. Bastos, Xiaonan Wang, Daniel Prins, Nicola K. Wilson, Carys Johnson, Kendig Sham, Michelle Wantoch, Sam Watcham, Sarah J. Kinston, Dean C. Pask, Tina L. Hamilton, Rachel Sneade, Amie K. Waller, Cedric Ghevaert, George S. Vassiliou, Elisa Laurenti, David G. Kent, Berthold Göttgens, Anthony R. Green
Journal: Blood (2022)

Adult hematopoietic stem cells (HSCs) are predominantly quiescent and can be activated in response to acute stress such as infection or cytotoxic insults. STAT1 is a pivotal downstream mediator of interferon (IFN) signaling and is required for IFN-induced HSC proliferation, but little is known about the role of STAT1 in regulating homeostatic hematopoietic stem/progenitor cells (HSPCs). Here, we show that loss of STAT1 altered the steady state HSPC landscape, impaired HSC function in transplantation assays, delayed blood cell regeneration following myeloablation, and disrupted molecular programs that protect HSCs, including control of quiescence. Our results also reveal STAT1-dependent functional HSC heterogeneity. A previously unrecognized subset of homeostatic HSCs with elevated major histocompatibility complex class II (MHCII) expression (MHCIIhi) displayed molecular features of reduced cycling and apoptosis and was refractory to 5-fluorouracil-induced myeloablation. Conversely, MHCIIlo HSCs displayed increased megakaryocytic potential and were preferentially expanded in CALR mutant mice with thrombocytosis. Similar to mice, high MHCII expression is a feature of human HSCs residing in a deeper quiescent state. Our results therefore position STAT1 at the interface of stem cell heterogeneity and the interplay between stem cells and the adaptive immune system, areas of broad interest in the wider stem cell field.
POS0412 ENHANCING SURVIVAL AND THERAPEUTIC EFFECT OF MESENCHYMAL STEM CELLS IN RAT MODEL OF RHEUMATOID ARTHRITIS VIA NANOMODIFICATION
Authors: Y. Lu, C. Ding
Journal: Annals of the Rheumatic Diseases (2022)

Background Mesenchymal stem cells (MSCs) have immunomodulatory, multilineage differentiation, and inflammatory/injury site-homing properties. These unique therapeutic features enable MSCs to be used in the treatment of rheumatoid arthritis (RA). However, MSCs therapy is still facing multiple obstacles in RA. First, MSCs are sensitive to inflammatory microenvironment (e.g., high level of reactive oxygen species [ROS]) and hence lose viability and immune regulatory effect when exposed in the inflamed joint. Second, uncontrolled differentiation of MSCs leads to the failure of cartilage repair. Objectives The aim of this study was to develop nanoparticle (NP)-modified MSCs that can maintain their biofunctions under the RA-associated oxidized stress and chondrogenically differentiate to repair cartilage. Methods Copper sulfide@manganese dioxide (CuS@MnO 2 ) NPs were sythesized, then modified with an MSC-targeting peptide ( V TAMEPG Q , termed VQ) and loaded with metformin (MET) to produce VQ-CuS@MnO 2 /MET (termed VCMM) NPs. After cellular uptake, the NP-modified VCMM-MSCs were obtained. The basic functions, chondrogenesis, anti-inflammatory effect and cell viability under oxidized stress of VCMM-MSCs were studied in vitro. Further, VCMM-MSCs were intravenously (i.v.) injected into rat models of collegan-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) to evaluate their survival and therapeutic effect in vivo. Results The NP-modified VCMM-MSCs exhibited stronger capabilities of cell migration and chondrogenesis relative to bare MSCs. VCMM-MSCs were also better than bare MSCs in terms of anti-inflammation towards lipopolysaccharide-induced M1 macrophages (RAW264.7). Moreover, VCMM-MSCs could survive under the RA-associated oxidized stress through catalyzing intracelluar ROS into oxygen by the superoxide dismutase (SOD)- and catalase (CAT)-like activities of the NPs, whereas approximately half of bare MSCs were dead. After i.v. injection into CIA and AIA rats, VCMM-MSCs lived longer and accumulated more abundant in the inflamed joints relative to bare MSCs (determined by in vivo fluorescence imaging). They promoted the repolarization of macrophages from M1 to M2 type in synovium, thereby inhibiting synovial inflammation in vivo. Further, VCMM-MSCs enhanced the sythesis of glycosaminoglycan and type II collegan in cartilage and thus promoted joint reapir. Conclusion The NP-modified VCMM-MSCs alleviated arthritis syndrome of both CIA and AIA models through reducing synovial hyperplasia and cartilage destruction. Nanomodification of MSCs may provide a new strategy to improve stem cell therapy in RA and other inflammatory diseases. Acknowledgements This study was supported by National Natural Science Foundation of China (81902198). Disclosure of Interests None declared.
AB0112 DECOY RECEPTOR 3 AND ITS SIGNAL PATHWAY CONTRIBUTE TO PATHOGENESIS IN ANKYLOSING SPONDYLITIS
Authors: Y. Jiang, S. B. Wang, X. Liao, Y. X. He, Y. F. Qing
Journal: Annals of the Rheumatic Diseases (2022)

Background Ankylosing spondylitis (AS) is a chronic progressive disease with invasion of spine and sacroiliac joint as the main clinical manifestation, which can be combined with systemic inflammation or abnormalities in multiple parts at the same time. There are complex changes of immune function in patients with AS, and its immune and genetic pathogenesis is still unclear. Decoy receptor 3 (DcR3), as a new immune molecule discovered in recent years, plays an important role in regulating T cell activation, proliferation, differentiation and apoptosis.Studies have confirmed that DcR3 is involved in the immune disorder process of rheumatoid arthritis, SLE, AS and other autoimmune diseases, so that the role of DcR3 in AS has attracted attention. However, the expression of DcR3 related pathway genes[1-3].However, studies evaluating the DcR3 related pathway genes in AS are scarce. Objectives To assess the contribution of DcR3 and its signal pathway to AS and the clinical importance of these genes in AS. Methods The mRNA expression levels of DCR3 and its signal pathway(DR3、TL1A、Fas、FasL、Ligth、LigthR、LTgthRNA expresured in peripheral blood mononuclear cells (PBMCs) from 50 AS patients and 50 healthy subjects. The relationship between DCR3 related molecular pathway expression levels and laboratory features was analyzed in AS patients. Results The expression levels of DCR3、DR3、Fas、Light were much lower in the AS group than in the HC groups (p&lt;0.05)(a,b,c,d), and the expression levels of LT The relationship between DCR3 related molecular pathway expression l Conclusion Compared with HC group, DCR3 and its signal pathway in PBMCs of AS patients are differentially expressed. It is speculated that DcR3 related molecular pathway gene may be involved in the pathogenesis of AS. Figure 1. Relative Expression of DcR3 related molecular pathway gene in the PBMCs of Patients. The mRNA levels in PBMCs from AS patients(n=50) and HCs(n=50) were measured by RT-qPCR. The expression levels of DCR3ˎDR3ˎFasˎLight were much lower in the AS group than in the HC groups (p&lt;0.05)(a,b,c,d), and the expression levels of LTβR was much higher in the AS group than in the HC groups (p&lt;0.05)(e). References [1]Lee CS, Hu CY, Tsai HF, et al. Elevated serum decoy receptor 3 with enhanced T cell activation in systemic lupus erythematosus. Clin Exp Immunol. 2008;151(3):383-390. doi:10.1111/j.1365-2249.2007.03579.x [2]Hayashi S, Miura Y, Tateishi K, Takahashi M, Kurosaka M. Decoy receptor 3 is highly expressed in patients with rheumatoid arthritis. Mod Rheumatol. 2010;20(1):63-68. doi:10.1007/s10165-009-0240-7. [3]Chen MH, Chen WS, Tsai CY, Liao HT, Chen CH, Chou CT. Overexpression of decoy receptor 3 in synovial tissues of inflammatory arthritis. Clin Exp Rheumatol. 2012;30(2):171-177. Acknowledgements Institute of Research Center of Gout and Hyperuricemia of the Affiliated Hospital, North Sichuan Medical College Disclosure of Interests None declared
AB1351 FULL LONGITUDINAL NAILFOLD VIDEOCAPILLAROSCOPY ANALYSIS OF MICROVASCULAR CHANGES DURING NORMAL PREGNANCY
Authors: G. Pacini, C. Schenone, A. Pogna, A. Ferraiolo, S. Ferrero, C. Gustavino, L. Carmisciano, C. Pizzorni, S. Paolino, E. Gotelli, A. Sulli, V. Smith, M. Cutolo
Journal: Annals of the Rheumatic Diseases (2022)

Background During pregnancy profound physiologic changes are required to ensure fetal development and meet maternal needs. Microvascular remodelling is one major responsible for pregnancy haemodynamic adaptation, still it is not routinely evaluated in the obstetric field [1–2]. Objectives To investigate the role of nailfold capillaroscopy (NCV) as a gold-standard and safe technique in detecting microvascular changes during normal pregnancy and to explore its possible application in clinical obstetric setting. Methods A population of 30 healthy pregnant women was longitudinally followed performing clinical assessment and NVC evaluation at each trimester and post-partum. Thirty non-pregnant age-matched healthy women having received at least two NVCs with a minimum 9 to 12-month interval were selected as controls. All NVC images were evaluated by a qualitative and semi-quantitative assessment using current standardised approach [3]. Statistical analyses were conducted to explore NVC parameters trend throughout gestation and its possible association with pregnancy course and clinical macrovascular parameters (i.e., systemic blood pressure, umbilical artery Doppler ultrasound). Results A progressive significant increase of capillary neoangiogenesis and a specular reduction in capillary dilations was observed during pregnancy ( p &lt;0.05). These statistically significant variations were not found in age-matched controls, who showed stable NVC parameters over a similar time frame ( p &lt;0.05). Not any significant association was found between NVC changes and pregnancy course, delivery outcome or macrovascular parameters. Conclusion This first comprehensive longitudinal NVC evaluation during normal pregnancy reports significant physiological microvascular variations throughout gestation, suggesting NVC as a safe and promising technique for further investigate and define patterns of microvascular changes in pregnant patients with rheumatic diseases. References [1]Thevissen et al. Expert Rev Med Devices. 2017;14(12):961–7. [2]Abdo et al. Physiol Res 2014;63:395–408. [3]Smith et al. Autoimmun Rev 2020; 19(3):102458. Disclosure of Interests None declared
AB0791 Madrid Sonographic Enthesis Index: useful outcome in the diagnosis of axial spondyloarthritis
Authors: C. S. Bellagha, M. Slouma, S. Ben Dhia, J. Ben Katib, L. Metoui, R. Dhahri, I. Gharsallah, B. Louzir
Journal: Annals of the Rheumatic Diseases (2022)

Background Madrid Sonographic Enthesis Index (MASEI) is an ultrasound (US) score for the evaluation of enthesis including inflammatory abnormalities and chronic damage in spondyloarthritis (SpA) [1]. This score includes bilaterally: plantar aponeurosis, Achilles tendon, distal and proximal patellar ligament, distal quadriceps, and brachial triceps tendons. Objectives We aimed to study the diagnosis value of MASEI score in axial spondyloarthritis. Methods We conducted a case-control study including 74 subjects divided into 2 groups: -G1: 37 patients fulfilling the Assessment of SpondyloArthritis international Society (ASAS) criteria for axial SA. -G0: 37 healthy controls matched for age and sex. Eight hundred eighty-eight entheses were assessed by a musculoskeletal experienced sonographer who was blinded to the clinical data concerning patients and controls. The MASEI was calculated for the 2 groups. For G1, we collected the following parameters: disease activity using Bath Ankylosing Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS-ESR). Statistical analysis was performed using “IBM SPASS Statistics” software version 21. A Receiver Operator Curve (ROC) analysis was performed to determine the cutoff of MASEI able to discriminate G0 from G1. Results The study included 29 men (78%) and 8 women (22%) in each group. The mean age was 44.51 ± 12.08 years. The mean age of onset was 38.06 ± 11.36 years. The mean disease evolution of 9.02 ± 7.83 years. The mean BASDAI and ASDAS-ESR were 4.47 ± 2.21 and 3.26 ± 1.31. MASEI score was significantly higher in patients compared to healthy controls (25.76 ± 9.8 versus 8.32 ± 6.65, p &lt;0.0001). A cutoff of 18 of the MASEI was able to distinguish G1 from G0 with a sensitivity of 81.1% and specificity of 91.9%. The air under curve (AUC) value was 0.920 (p&lt;0.0001). No correlation was found between MASEI and BASDAI, and ASDAS-ESR. Conclusion Our study showed that MASEI score is significantly higher in SpA patients and seems to have a diagnostic accuracy. Besides, MASEI was able to distinguish between SpA patients and healthy controls with a cut-off of 18. Those results agree with the findings of other researchers in the field [2]. References [1]de Miguel E, Cobo T, Muñoz-Fernández S, Naredo E, Usón J, Acebes JC, et al. Validity of enthesis ultrasound assessment in spondyloarthropathy. Ann Rheum Dis. févr 2009;68(2):169‑74. [2]Ebstein E, Coustet B, Masson-Behar V, Forien M, Palazzo E, Dieudé P, et al. Enthesopathy in rheumatoid arthritis and spondyloarthritis: An ultrasound study. Joint Bone Spine. oct 2018;85(5):577‑81. Disclosure of Interests None declared
AB0860 Repercussions of tobacco on spondyloarthritis: the Iceberg effect!
Authors: L. Kharrat, M. Slouma, A. Abdennadher, K. Amri, Y. Mallat, L. Metoui, R. Dhahri, I. Gharsallah, B. Louzir
Journal: Annals of the Rheumatic Diseases (2022)

Background The deleterious effect of smoking is frequently studied in inflammatory diseases such as spondyloarthritis (SA) [1]. Objectives The objective of our study was to identify the consequences of smoking during AS. Methods We conducted a cross sectional study including patients followed for spondyloarthritis meeting the ASAS 2009 criteria. For each patient we collected the following parameters: age, age at onset of the disease, duration of progression, disease activity using BASDAI and ASDAS-CRP scores and structural damage using BASRI and mSASSS scores. We also measured sedimentation rate (ESR) and C-reactive protein (CRP). Statistical analysis was performed using SPSS software. Results We included 140 patients. Seventy-three percent were male (n=102). The mean age was 43 ± 12.9 years. The age of onset of the disease was 34.28 ± 12 years. The mean disease duration was 110 ± 107.8 months. Sixty patients were smokers (43%) at an average of 20.75 ± 16.09 pack-years. Mean ESR and CRP were 36.49 ± 27.22 mm and 29 ± 44.27 mg/L, respectively. The mean BASDAI and ASDAS-CRP were 3.68 ± 1.86 and 2.99 ± 0.98, respectively. The mean BASRI and mSASSS were 4.12 ± 3 and 10.26 ± 15.41, respectively. Smokers had significantly higher BASRI and mSASSS scores (BASRI: 5.02 ± 3.32 vs 3.47 ± 2.6; p=0.005 and mSASSS: 14.07 ± 17.56 vs 7.02 ± 12 .62; p=0.03). In addition, the number of packets year was correlated to mSASSS (r=0.399; p=0.01). On the other hand, we did not find any association between smoking and the following parameters: ESR, CRP, BASDAI or ASDAS-CRP. Conclusion As reported in other studies, ours’ showed that structural damage was correlated with the number of pack-years [2]. Smoking was associated with this structural damage in SA regardless the inflammatory biomarkers and the disease activity. This suggests that control of structural damage in SA requires smoking cessation. References [1]Zhao SS, Goodson NJ, Robertson S, Gaffney K. Smoking in spondyloarthritis: unravelling the complexities. Rheumatology. 1 juill 2020;59(7):1472‑81. [2]Wendling D, Prati C. Spondyloarthritis and smoking: towards a new insight into the disease. Expert Rev Clin Immunol. juin 2013;9(6):511‑6. Disclosure of Interests None declared
AB0863 Emergence of spondyloarthritis following B cell-depleting monoclonal antibody therapy for multiple sclerosis
Authors: T. Pham, P. Caroline, P. Lafforgue, C. Barral, A. Maarouf, J. Pelletier, A. Rico, B. Audoin
Journal: Annals of the Rheumatic Diseases (2022)

Background Anti-CD20 B-cell-depleting therapies, including rituximab and ocrelizumab, have demonstrated their efficacy in patients with relapsing–remitting multiple sclerosis (RRMS). Objectives Herein we report a series of patients with RRMS treated with anti-CD20 monoclonal antibodies (mAb) who developed a de novo spondyloarthritis (SpA). Methods Following the presentation of an index case, we collected all cases of de novo SpA in the anti-CD20-treated RRMS cohort of our institution’s referral center. Clinical, biochemical, and imaging characteristics of the cases were identified through a clinical assessment. Information was collected via a standardized form to obtain key characteristics on the onset and type of disease development at baseline and on outcomes up to 12 months. All patients had a magnetic resonance imaging (MRI) of the sacroiliac joints and, depending on the clinical presentation, a spine MRI and/or a musculoskeletal grayscale and power Doppler (PD) ultrasound (US) examination. Results De novo SpA developed in 6 of 480 patients with RRMS treated with anti-CD20 mAb, accounting for an incidence of 1.25%. All but one received rituximab treatment. The median time from the last anti-CD20 mAb infusion to SpA onset was 1.5 months [IQR: 1-4]. At the time of SpA emergence, the RRMS activity was controlled. The most frequent clinical SpA phenotype identified was peripheral SpA (4/6), with Power Doppler ultrasound-detected synovitis. The 2 patients with axial SpA phenotype had bilateral sacroiliitis on MRI. Five of the 6 patients had a personal or family history of psoriasis, whereas the prevalence of psoriasis in the entire RRMS cohort was 3.33% (16/480). No other extra-articular manifestation was observed. All patients were HLA B27 negative and fulfilled at least one classification criteria of SpA. None required hospitalization and the SpA onset did not affect the management of MS. The 2 patients with axial SpA were successfully treated with NSAIDs. Among the patients with peripheral SpA, 3 of four had inadequate response to NSAIDs, 2 were treated with methotrexate and 1 with leflunomide. Only one patient required initiation of an IL-17 inhibitor to control the SpA activity. Conclusion We report a pattern of patients with MS successfully treated with B cell-depleting drug developing axial or peripheral SpA, predominantly HLA-B27 negativity and associated with psoriasis. Disclosure of Interests None declared